Diisopropylethylamine → 10-[(4-Tert-butylphenoxy)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamide

HRID 2244288Notes

Reaction equation

HRID 2244288 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[N:20]3[C:14]([CH2:15][NH:16][C:17]4[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=4[CH2:19]3)=[CH:13][CH:12]=2)=[O:10])[CH:2]=1.C(N(CC)C(C)C)(C)C.[C:34]([C:38]1[CH:48]=[CH:47][C:41]([O:42][CH2:43][C:44](Cl)=[O:45])=[CH:40][CH:39]=1)([CH3:37])([CH3:36])[CH3:35]>O1CCCC1>[C:34]([C:38]1[CH:48]=[CH:47][C:41]([O:42][CH2:43][C:44]([N:16]2[C:17]3[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=3[CH2:19][N:20]3[C:11]([C:9]([NH:8][CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[O:10])=[CH:12][CH:13]=[C:14]3[CH2:15]2)=[O:45])=[CH:40][CH:39]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6111954-tert-Butylphenoxyacetyl chlorideHCID 22053658N-(3-Pyridinylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

Product 1

HCID 6868681710-[(4-Tert-butylphenoxy)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamideYield 58.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 76, Step C (0.300 g, 0.942 mmol), and N,N-diisopropylethylamine (0.26 mL, 1.508 mmol) in dry tetrahydrofuran (10 mL) was added dropwise 4-tert-butylphenoxyacetyl chloride (0.32 g, 1.41 mmol) and the reaction mixture was stirred at room temperature under nitrogen for 21 hours. The reaction was then quenched by the addition of 2 M sodium hydroxide (5 mL) and the mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The organic phase was separated, washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford a yellow foam. Purification by flash chromatography using a solvent gradient of 0 to 4% methanol in dichloromethane gave a colorless syrup that was triturated with diethyl ether to afford the title compound (0.280 g, 58%) as a white solid, m.p. 85° C.

Workup

  1. customThe reaction was then quenched by the addition of 2 M sodium hydroxide (5 mL)
  2. customthe mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL)
  3. customThe organic phase was separated
  4. washwashed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow foam
  8. customPurification by flash chromatography
  9. customgave a colorless syrup that
  10. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-2ea83f27de7c40258ebf87ccedd4bfe9
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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